Search results for: cerebral malaria
282 Neuroprotective Effect of Vildagliptin against Cerebral Ischemia in Rats
Authors: Salma A. El-Marasy, Rehab F. Abdel-Rahman, Reham M. Abd-Elsalam
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The burden of stroke is intensely increasing worldwide. Brain injury following transient or permanent focal cerebral ischemia develops ischemic stroke as a consequence of a complex series of pathophysiological events. The aim of this study is to evaluate the possible neuroprotective effect of a dipeptidyl peptidase-4 inhibitor, vildagliptin, independent on its insulinotropic properties in non-diabetic rats subjected to cerebral ischemia. Anaesthetized Wistar rats were subjected to either left middle cerebral artery occlusion (MCAO) or sham operation followed by reperfusion after 30 min of MCAO. The other three groups were orally administered vildagliptin at 3 dose levels (2.5, 5, 10 mg/kg) for 3 successive weeks before subjected to left focal cerebral ischemia/reperfusion and till the end of the study. Neurological deficit scores and motor activity were assessed 24h following reperfusion. 48h following reperfusion, rats were euthanized and their left brain hemispheres were harvested and used in the biochemical, histopathological, and immunohistochemical investigations. Vildagliptin pretreatment improved neurological score deficit, locomotor activity and motor coordination in MCAO rats. Moreover, vildagliptin reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), phosphotylinosital 3 kinase (PI3K), phosphorylated of protein kinase B (p-AKT), and mechanistic target of rapamycin (mTOR) brain contents in addition to reducing protein expression of caspase-3. Also, vildagliptin showed a dose-dependent attenuation in neuronal cell loss and histopathological alterations in MCAO rats. This study proves that vildagliptin exerted the neuroprotective effect in a dose-dependent manner as shown in amelioration of neuronal cell loss and histopathological damage in MCAO rats, which may be mediated by attenuating neuronal and motor deficits, it’s anti-oxidant property, activation of PI3K/AKT/mTOR pathway and its anti-apoptotic effect.Keywords: caspase-3, cerebral ischemia, dipeptidyl peptidase-4 inhibitor, oxidative stress, PI3K/AKT/mTOR pathway, rats, vildagliptin
Procedia PDF Downloads 155281 Construction of a Dynamic Migration Model of Extracellular Fluid in Brain for Future Integrated Control of Brain State
Authors: Tomohiko Utsuki, Kyoka Sato
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In emergency medicine, it is recognized that brain resuscitation is very important for the reduction of mortality rate and neurological sequelae. Especially, the control of brain temperature (BT), intracranial pressure (ICP), and cerebral blood flow (CBF) are most required for stabilizing brain’s physiological state in the treatment for such as brain injury, stroke, and encephalopathy. However, the manual control of BT, ICP, and CBF frequently requires the decision and operation of medical staff, relevant to medication and the setting of therapeutic apparatus. Thus, the integration and the automation of the control of those is very effective for not only improving therapeutic effect but also reducing staff burden and medical cost. For realizing such integration and automation, a mathematical model of brain physiological state is necessary as the controlled object in simulations, because the performance test of a prototype of the control system using patients is not ethically allowed. A model of cerebral blood circulation has already been constructed, which is the most basic part of brain physiological state. Also, a migration model of extracellular fluid in brain has been constructed, however the condition that the total volume of intracranial cavity is almost changeless due to the hardness of cranial bone has not been considered in that model. Therefore, in this research, the dynamic migration model of extracellular fluid in brain was constructed on the consideration of the changelessness of intracranial cavity’s total volume. This model is connectable to the cerebral blood circulation model. The constructed model consists of fourteen compartments, twelve of which corresponds to perfused area of bilateral anterior, middle and posterior cerebral arteries, the others corresponds to cerebral ventricles and subarachnoid space. This model enable to calculate the migration of tissue fluid from capillaries to gray matter and white matter, the flow of tissue fluid between compartments, the production and absorption of cerebrospinal fluid at choroid plexus and arachnoid granulation, and the production of metabolic water. Further, the volume, the colloid concentration, and the tissue pressure of/in each compartment are also calculable by solving 40-dimensional non-linear simultaneous differential equations. In this research, the obtained model was analyzed for its validation under the four condition of a normal adult, an adult with higher cerebral capillary pressure, an adult with lower cerebral capillary pressure, and an adult with lower colloid concentration in cerebral capillary. In the result, calculated fluid flow, tissue volume, colloid concentration, and tissue pressure were all converged to suitable value for the set condition within 60 minutes at a maximum. Also, because these results were not conflict with prior knowledge, it is certain that the model can enough represent physiological state of brain under such limited conditions at least. One of next challenges is to integrate this model and the already constructed cerebral blood circulation model. This modification enable to simulate CBF and ICP more precisely due to calculating the effect of blood pressure change to extracellular fluid migration and that of ICP change to CBF.Keywords: dynamic model, cerebral extracellular migration, brain resuscitation, automatic control
Procedia PDF Downloads 156280 The Impact of Artesunate-Amodiaquine on Schistosoma mansoni Infection among Children Infected by Plasmodium in Rural Area of Lemfu, Kongo Central, Democratic Republic of the Congo
Authors: Mbanzulu Kennedy, Zanga Josue, Wumba Roger
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Malaria and schistosomiasis remain life-threatening public health problems in sub-Saharan Africa. The infection pattern related to age indicates that preschool and school-age children are at the highest risk of malaria and schistosomiasis. Both parasitic infections, separately or combined, may have negative impacts on the haemoglobin concentration levels. The existing data revealed that artemisinin derivatives commonly used to cure malaria present also in antischistosomal activities. The current study investigated the impact of Artesunate-Amodiaquine (AS-AQ) on schistosomiasis when administered to treat malaria in rural area of Lemfu, DRC. A prospective longitudinal study including 171 coinfected children screened for anaemia, Schistosoma mansoni, and Plasmodium falciparum infections. The egg reduction rate and haemoglobin concentration were assessed four weeks after the treatment with AS-AQ, of all coinfected children of this series. One hundred and twenty-five (74.4%) out of 168 coinfected children treated and present during the assessment were found stool negative for S. mansoni eggs. Out of 43 (25.6%) children who remained positives, 37 (22%) showed a partial reduction of eggs amount, and no reduction was noted in 3.6% of coinfected. The mean of haemoglobin concentration and the prevalence of anaemia were, respectively, 10.74±1.5g/dl , 11.2±1.3g/dl, and 64.8%, 51.8%, respectively, before and after treatment, p<0.001. The AS-AQ commonly used against Plasmodium allowed curing S. mansoni in coinfected children and increasing the Hb level. For the future, the randomized and multicentric clinical trials are needed for a better understanding of the effectiveness of AS-AQ against Schistosoma spp. The trial registration number was 3487183.Keywords: paludisme, schistosomiase, as-aq, enfants lemfu
Procedia PDF Downloads 102279 Exploring the Gap between Coverage, Access, Utilization of Long Lasting Insecticidal Nets (LLINs) among the People of Malaria Endemic Districts in Bangladesh
Authors: Fouzia Khanam, Tridib Chowdhury, Belal Hossain, Sajedur Rahman, Mahfuzar Rahman
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Introduction: Over the last decades, the world has achieved a noticeable success in preventing malaria. Nevertheless, malaria, a vector-borne infectious disease, remains a major public health burden globally as well as in Bangladesh. To achieve the goal of eliminating malaria, BRAC, a leading organization of Bangladesh in collaboration with government, is distributing free LLIN to the 13 endemic districts of the country. The study was conducted with the aim of assessing the gap between coverage, access, and utilization of LLIN among the people of the 13 malaria endemic districts of Bangladesh. Methods: This baseline study employed a community cross-sectional design triangulated with qualitative methods to measure households’ ownership, access and use of 13 endemic districts. A multistage cluster random sampling was employed for the quantitative part and for qualitative part a purposive sampling strategy was done. Thus present analysis included 2640 households encompassing a total of 14475 populations. Data were collected using a pre-tested structured questionnaire through one on one face-to-face interview with respondents. All analyses were performed using STATA (Version 13.0). For the qualitative part participant observation, in-depth interview, focus group discussion, key informant interview and informal interview was done to gather the contextual data. Findings: According to our study, 99.8% of households possessed at least one-bed net in both study areas. 77.4% households possessed at least two LLIN and 43.2% households had access to LLIN for all the members. So the gap between coverage and access is 34%. 91.8% people in the 13 districts and 95.1% in Chittagong Hill Tracts areas reported having had slept under a bed net the night before interviewed. And despite the relatively low access, in 77.8% of households, all the members were used the LLIN the previous night. This higher utilization compared to access might be due to the increased awareness among the community people regarding LLIN uses. However, among those people with sufficient access to LLIN, 6% of them still did not use the LLIN which reflects the behavioral failure that needs to be addressed. The major reasons for not using LLIN, identified by both qualitative and quantitative findings, were insufficient access, sleeping or living outside the home, migration, perceived low efficacy of LLIN, fear of physical side effects or feeling uncomfortable. Conclusion: Given that LLIN access and use was a bit short of the targets, it conveys important messages to the malaria control program. Targeting specific population segments and groups for achieving expected LLIN coverage is very crucial. And also, addressing behavior failure by well-designed behavioral change interventions is mandatory.Keywords: long lasting insecticide net, malaria, malaria control programme, World Health Organisation
Procedia PDF Downloads 187278 The Lived Experiences of Fathers with Children Who Have Cerebral Palsy: An Interpretative Phenomenological Analysis
Authors: Krizette Ladera
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Fathers are there not only to provide the financial stability of a family but a father is also there to provide the love and support that usually people would see as the mother’s responsibility. To describe the lived experiences and how fathers make sense of their lived experiences with their children who have cerebral palsy is the main objective of the study. A qualitative research using a thematic analysis was used for the study. The qualitative research focused on the personal narratives, self-report and expression of the participant’s memory in terms of how they tell their stories. The interpretative phenomenological analysis was used to focus on the experience of the participants on how they will describe their experiences, and to also add on that the IPA will also attempt to describe and explain the meaning of human experiences using interview, specifically on the father who have a child that suffers from cerebral palsy. For the sampling technique, the snowball technique was used to gather participants from the referral of other participants. The five non-randomly selected fathers will be served as the participants for the research. A self-made interview with an open-ended question was used as the research instrument; it includes profiling of the respondent as well as their experiences in taking care of their child that suffers from cerebral palsy. In analyzing a data, the researcher used the thematic analysis where in the interview was made into a transcript, then it was organized and divided themes. After that, the relations of each themes, was identified and it was later documented and translated into written text format using thematic grouping. Finally, the researcher analyzed each data according to its themes and put it in a table to be presented in the result section of the study And as for the result of the study, the researcher was able to come up with the four (4) main themes that most of the participants experienced and those are: The experiences in finding out about the condition of the Child, disclosing the condition of the child to the family and its emotional effect, The experiences of living the day of day realities in providing the physical, financial, emotional and a well balanced environment to the child, and the religious perspectives of the fathers. Along with those four (4) themes comes the subtheme which explains the themes in a more detailed explanation.Keywords: cerebral palsy, children, fathers, lived experiences
Procedia PDF Downloads 205277 Thermoelectric Blanket for Aiding the Treatment of Cerebral Hypoxia and Other Related Conditions
Authors: Sarayu Vanga, Jorge Galeano-Cabral, Kaya Wei
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Cerebral hypoxia refers to a condition in which there is a decrease in oxygen supply to the brain. Patients suffering from this condition experience a decrease in their body temperature. While there isn't any cure to treat cerebral hypoxia as of date, certain procedures are utilized to help aid in the treatment of the condition. Regulating the body temperature is an example of one of those procedures. Hypoxia is well known to reduce the body temperature of mammals, although the neural origins of this response remain uncertain. In order to speed recovery from this condition, it is necessary to maintain a stable body temperature. In this study, we present an approach to regulating body temperature for patients who suffer from cerebral hypoxia or other similar conditions. After a thorough literature study, we propose the use of thermoelectric blankets, which are temperature-controlled thermal blankets based on thermoelectric devices. These blankets are capable of heating up and cooling down the patient to stabilize body temperature. This feature is possible through the reversible effect that thermoelectric devices offer while behaving as a thermal sensor, and it is an effective way to stabilize temperature. Thermoelectricity is the direct conversion of thermal to electrical energy and vice versa. This effect is now known as the Seebeck effect, and it is characterized by the Seebeck coefficient. In such a configuration, the device has cooling and heating sides with temperatures that can be interchanged by simply switching the direction of the current input in the system. This design integrates various aspects, including a humidifier, ventilation machine, IV-administered medication, air conditioning, circulation device, and a body temperature regulation system. The proposed design includes thermocouples that will trigger the blanket to increase or decrease a set temperature through a medical temperature sensor. Additionally, the proposed design allows an efficient way to control fluctuations in body temperature while being cost-friendly, with an expected cost of 150 dollars. We are currently working on developing a prototype of the design to collect thermal and electrical data under different conditions and also intend to perform an optimization analysis to improve the design even further. While this proposal was developed for treating cerebral hypoxia, it can also aid in the treatment of other related conditions, as fluctuations in body temperature appear to be a common symptom that patients have for many illnesses.Keywords: body temperature regulation, cerebral hypoxia, thermoelectric, blanket design
Procedia PDF Downloads 159276 The Use of Vasopressin in the Management of Severe Traumatic Brain Injury: A Narrative Review
Authors: Nicole Selvi Hill, Archchana Radhakrishnan
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Introduction: Traumatic brain injury (TBI) is a leading cause of mortality among trauma patients. In the management of TBI, the main principle is avoiding cerebral ischemia, as this is a strong determiner of neurological outcomes. The use of vasoactive drugs, such as vasopressin, has an important role in maintaining cerebral perfusion pressure to prevent secondary brain injury. Current guidelines do not suggest a preferred vasoactive drug to administer in the management of TBI, and there is a paucity of information on the therapeutic potential of vasopressin following TBI. Vasopressin is also an endogenous anti-diuretic hormone (AVP), and pathways mediated by AVP play a large role in the underlying pathological processes of TBI. This creates an overlap of discussion regarding the therapeutic potential of vasopressin following TBI. Currently, its popularity lies in vasodilatory and cardiogenic shock in the intensive care setting, with increasing support for its use in haemorrhagic and septic shock. Methodology: This is a review article based on a literature review. An electronic search was conducted via PubMed, Cochrane, EMBASE, and Google Scholar. The aim was to identify clinical studies looking at the therapeutic administration of vasopressin in severe traumatic brain injury. The primary aim was to look at the neurological outcome of patients. The secondary aim was to look at surrogate markers of cerebral perfusion measurements, such as cerebral perfusion pressure, cerebral oxygenation, and cerebral blood flow. Results: Eight papers were included in the final number. Three were animal studies; five were human studies, comprised of three case reports, one retrospective review of data, and one randomised control trial. All animal studies demonstrated the benefits of vasopressors in TBI management. One animal study showed the superiority of vasopressin in reducing intracranial pressure and increasing cerebral oxygenation over a catecholaminergic vasopressor, phenylephrine. All three human case reports were supportive of vasopressin as a rescue therapy in catecholaminergic-resistant hypotension. The retrospective review found vasopressin did not increase cerebral oedema in TBI patients compared to catecholaminergic vasopressors; and demonstrated a significant reduction in the requirements of hyperosmolar therapy in patients that received vasopressin. The randomised control trial results showed no significant differences in primary and secondary outcomes between TBI patients receiving vasopressin versus those receiving catecholaminergic vasopressors. Apart from the randomised control trial, the studies included are of low-level evidence. Conclusion: Studies favour vasopressin within certain parameters of cerebral function compared to control groups. However, the neurological outcomes of patient groups are not known, and animal study results are difficult to extrapolate to humans. It cannot be said with certainty whether vasopressin’s benefits stand above usage of other vasoactive drugs due to the weaknesses of the evidence. Further randomised control trials, which are larger, standardised, and rigorous, are required to improve knowledge in this field.Keywords: catecholamines, cerebral perfusion pressure, traumatic brain injury, vasopressin, vasopressors
Procedia PDF Downloads 67275 Numerical Study on the Hazards of Gravitational Forces on Cerebral Aneurysms
Authors: Hashem M. Alargha, Mohammad O. Hamdan, Waseem H. Aziz
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Aerobatic and military pilots are subjected to high gravitational forces that could cause blackout, physical injuries or death. A CFD simulation using fluid-solid interactions scheme has been conducted to investigate the gravitational effects and hazards inside cerebral aneurysms. Medical data have been used to derive the size and geometry of a simple aneurysm on a T-shaped bifurcation. The results show that gravitational force has no effect on maximum Wall Shear Stress (WSS); hence, it will not cause aneurysm initiation/formation. However, gravitational force cause causes hypertension which could contribute to aneurysm rupture.Keywords: aneurysm, cfd, wall shear stress, gravity, fluid dynamics, bifurcation artery
Procedia PDF Downloads 367274 Measuring the Effect of Continuous Performance Test-3 Administration on Regional Cerebral Blood Flow with Single-Photon Emission Computed Tomography in Adult ADHD
Authors: Claire Stafford, Charles Golden, Daniel Amen, Kristen Willeumier
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The aim of this study is to investigate the effect of the administration of the Conners Continuous Performance Test (CPT-3) on cerebral blood flow (CBF) in adults with ADHD. The data for this study was derived from a large SPECT database. Participants in the ADHD group (n=81, Mage=37.97) were similar to those in the healthy control group (n=8503, Mage=41.86). All participants were assessed for cerebral blood flow levels before and after CPT-3 administration. Both age and gender were considered covariates. Multiple 2-by-2 ANCOVAs with repeated measures were conducted with sphericity assumed. The main effects of CPT-3 administration on CBF levels were significant in the left and right side of the frontal and occipital, and right temporal lobe. The main effects of ADHD diagnosis were significant in all brain areas assessed. The interaction between CPT-3 administration and ADHD diagnosis was significant in the left and right side of the limbic system, basal ganglia, the frontal lobe, and occipital lobe. Post hoc tests with a Bonferroni adjustment revealed that CBF levels increased following CPT-3 administration but less so in the ADHD group. Individuals had higher levels of CBF following the administration of CPT-3. Due to a significant interaction, we can infer that ADHD diagnosis changes the effect of CPT-3 administration on CBF levels. This is consistent with our hypothesis considering that CPT-3 is a test of sustained attention, a common challenge for children with ADHD. The aforementioned interaction was not found to be significant in the parietal lobe. This may be due to the nature of CPT- 3 which does not require an integration of sensory information.Keywords: SPECT, ADHD, conners continuous performance test, cerebral blood flow
Procedia PDF Downloads 101273 A Two Arm Double Parallel Randomized Controlled Trail of the Effects of Health Education Intervention on Insecticide Treated Nets Use and Its Practices among Pregnant Women Attending Antenatal Clinic: Study Protocol
Authors: Opara Monica, Suriani Ismail, Ahmad Iqmer Nashriq Mohd Nazan
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The true magnitude of the mortality and morbidity attributable to malaria worldwide is, at best, a scientific guess, although it is not disputable that the greatest burden is in sub-Saharan Africa. Those at highest risk are children younger than 5 years and pregnant women, particularly primigravidae. Nationally, malaria remains the third leading cause of death and is still considered a major public health problem. Therefore, this study is aimed to assess the effectiveness of health education intervention on insecticide-treated net use and its practices among pregnant women attending antenatal clinics. Materials and Methods: This study will be an intervention study with two arms double parallel randomized controlled trial (blinded) to be conducted in 3 stages. The first stage will develop health belief model (HBM) program, while in the second stage, pregnant women will be recruited, assessed (baseline data), randomized into two arms of the study, and follow-up for six months. The third stage will evaluate the impact of the intervention on HBM and disseminate the findings. Data will be collected with the use of a structured questionnaire which will contain validated tools. The main outcome measurement will be the treatment effect using HBM, while data will be analysed using SPSS, version 22. Discussion: The study will contribute to the existing knowledge on hospital-based care programs for pregnant women in developing countries where the literature is scanty. It will generally give insight into the importance of HBM measurement in interventional studies on malaria and other related infectious diseases in this setting.Keywords: malaria, health education, insecticide-treated nets, sub-Saharan Africa
Procedia PDF Downloads 122272 Functioning of a Temporarily Single Parent Family System Due to Migration from the Perspective of Adolescents with Cerebral Palsy
Authors: A. Gagat-Matuła
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There is a definite lack – in Poland, as well as around the world – of empirical studies of families raising handicapped child, in which one parent migrates. In diagnostics of the functioning of such families emphasis should be placed not only on the difficulties, but most of all it should be indicated what possibilities are there for the family and how it overcomes the difficulties. Migration of a parent on the one hand is a chance to improve the family’s material situation. In certain circumstances this may only be an “escape” into work from the issues associated with the upbringing and rehabilitation of a handicapped child. The aim of the study was to learn the functioning of a temporarily single parent family system as a result of migration of a parent from the perspective of adolescents with cerebral palsy. The study was conducted in the year 2013 in the area of Eastern Poland. It involved an analysis of 70 persons (with cerebral palsy in an intellectual capacity) from families in which at least one of the parents migrates. The study incorporated the diagnostic survey method. These tools were used: Family Evaluation Scales (SOR) adapted for Poland by Andrzej Margasiński. The explorations in this study indicate, that 47% of studied temporarily single parent families are balanced models. This is evidence of the resources at the disposal of the family which, despite the disability of the child and temporary separation, is able to function properly. The conducted studies show, that 37% of temporarily single parent families are imbalanced models in the perception of adolescents with cerebral palsy. These families experience functional difficulties and require psychological and pedagogical support. There is a need for building skills related to effective coping with family stress. Especially considering, that families of an imbalanced type do not use the internal and external resources of the family system. Such a situation may deepen the disarrangement of family life. In intermediate families (16%) there are also temporary difficulties in functioning. Separation anxiety experienced by mothers may disrupt relations and introduce additional stress factors. For that reason it is important to provide support for women with difficulties coping with the emotions associated with raising handicapped adolescents and migratory separation.Keywords: child with cerebral palsy, family, migration, parents
Procedia PDF Downloads 419271 Utility of CT Perfusion Imaging for Diagnosis and Management of Delayed Cerebral Ischaemia Following Subarachnoid Haemorrhage
Authors: Abdalla Mansour, Dan Brown, Adel Helmy, Rikin Trivedi, Mathew Guilfoyle
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Introduction: Diagnosing delayed cerebral ischaemia (DCI) following aneurysmal subarachnoid haemorrhage (SAH) can be challenging, particularly in poor-grade patients. Objectives: This study sought to assess the value of routine CTP in identifying (or excluding) DCI and in guiding management. Methods: Eight-year retrospective neuroimaging study at a large UK neurosurgical centre. Subjects included a random sample of adult patients with confirmed aneurysmal SAH that had a CTP scan during their inpatient stay, over a 8-year period (May 2014 - May 2022). Data collected through electronic patient record and PACS. Variables included age, WFNS scale, aneurysm site, treatment, the timing of CTP, radiologist report, and DCI management. Results: Over eight years, 916 patients were treated for aneurysmal SAH; this study focused on 466 patients that were randomly selected. Of this sample, 181 (38.84%) had one or more CTP scans following brain aneurysm treatment (Total 318). The first CTP scan in each patient was performed at 1-20 days following ictus (median 4 days). There was radiological evidence of DCI in 83, and no reversible ischaemia was found in 80. Findings were equivocal in the remaining 18. Of the 103 patients treated with clipping, 49 had DCI radiological evidence, in comparison to 31 of 69 patients treated with endovascular embolization. The remaining 9 patients are either unsecured aneurysms or non-aneurysmal SAH. Of the patients with radiological evidence of DCI, 65 had a treatment change following the CTP directed at improving cerebral perfusion. In contrast, treatment was not changed for (61) patients without radiological evidence of DCI. Conclusion: CTP is a useful adjunct to clinical assessment in the diagnosis of DCI and is helpful in identifying patients that may benefit from intensive therapy and those in whom it is unlikely to be effective.Keywords: SAH, vasospasm, aneurysm, delayed cerebral ischemia
Procedia PDF Downloads 68270 Validating the Cerebral Palsy Quality of Life for Children (CPQOL-Child) Questionnaire for Use in Sri Lanka
Authors: Shyamani Hettiarachchi, Gopi Kitnasamy
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Background: The potentially high level of physical need and dependency experienced by children with cerebral palsy could affect the quality of life (QOL) of the child, the caregiver and his/her family. Poor QOL in children with cerebral palsy is associated with the parent-child relationship, limited opportunities for social participation, limited access to healthcare services, psychological well-being and the child's physical functioning. Given that children experiencing disabilities have little access to remedial support with an inequitable service across districts in Sri Lanka, and given the impact of culture and societal stigma, there may be differing viewpoints across respondents. Objectives: The aim of this study was to evaluate the psychometric properties of the Tamil version of the Cerebral Palsy Quality of Life for Children (CPQOL-Child) Questionnaire. Design: An instrument development and validation study. Methods: Forward and backward translations of the CPQOL-Child were undertaken by a team comprised of a physiotherapist, speech and language therapist and two linguists for the primary caregiver form and the child self-report form. As part of a pilot phase, the Tamil version of the CPQOL was completed by 45 primary caregivers with children with cerebral palsy and 15 children with cerebral palsy (GMFCS level 3-4). In addition, the primary caregivers commented on the process of filling in the questionnaire. The psychometric properties of test-retest reliability, internal consistency and construct validity were undertaken. Results: The test-retest reliability and internal consistency were high. A significant association (p < 0.001) was found between limited motor skills and poor QOL. The Cronbach's alpha for the whole questionnaire was at 0.95.Similarities and divergences were found between the two groups of respondents. The child respondents identified limited motor skills as associated with physical well-being and autonomy. Akin to this, the primary caregivers associated the severity of motor function with limitations of physical well-being and autonomy. The trend observed was that QOL was not related to the level of impairment but connected to environmental factors by the child respondents. In addition to this, the main concern among primary caregivers about the child's future and on the child's lack of independence was not fully captured by the QOL questionnaire employed. Conclusions: Although the initial results of the CPQOL questionnaire show high test-retest reliability and internal consistency of the instrument, it does not fully reflect the socio-cultural realities and primary concerns of the caregivers. The current findings highlight the need to take child and caregiver perceptions of QOL into account in clinical practice and research. It strongly indicates the need for culture-specific measures of QOL.Keywords: cerebral palsy, CPQOL, culture, quality of life
Procedia PDF Downloads 343269 Combating Malaria: A Drug Discovery Approach Using Thiazole Derivatives Against Prolific Parasite Enzyme PfPKG
Authors: Hari Bezwada, Michelle Cheon, Ryan Divan, Hannah Escritor, Michelle Kagramian, Isha Korgaonkar, Maya MacAdams, Udgita Pamidigantam, Richard Pilny, Eleanor Race, Angadh Singh, Nathan Zhang, LeeAnn Nguyen, Fina Liotta
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Malaria is a deadly disease caused by the Plasmodium parasite, which continues to develop resistance to current antimalarial drugs. In this research project, the effectiveness of numerous thiazole derivatives was explored in inhibiting the PfPKG, a crucial part of the Plasmodium life cycle. This study involved the synthesis of six thiazole-derived amides to inhibit the PfPKG pathway. Nuclear Magnetic Resonance (NMR) spectroscopy and Infrared (IR) spectroscopy were used to characterize these compounds. Furthermore, AutoDocking software was used to predict binding affinities of these thiazole-derived amides in silico. In silico, compound 6 exhibited the highest predicted binding affinity to PfPKG, while compound 5 had the lowest affinity. Compounds 1-4 displayed varying degrees of predicted binding affinity. In-vitro, it was found that compound 4 had the best percent inhibition, while compound 5 had the worst percent inhibition. Overall, all six compounds had weak inhibition (approximately 30-39% at 10 μM), but these results provide a foundation for future drug discovery experiments.Keywords: Medicinal Chemistry, Malaria, drug discovery, PfPKG, Thiazole, Plasmodium
Procedia PDF Downloads 98268 Awareness Creation of Benefits of Antitrypsin-Free Nutraceutical Biopowder for Increasing Human Serum Albumin Synthesis as Possible Adjunct for Management of MDRTB or MDRTB-HIV Patients
Authors: Vincent Oghenekevbe Olughor, Olusoji Mayowa Ige
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Except for a preexisting liver disease and malnutrition, there are no predilections for low serum albumin (SA) levels in humans. At normal reference levels (4.0-6.0g/dl) SA is a universal marker for mortality and morbidity risks assessments where depletion by 1.0g/dl increases mortality risk by 137% and morbidity by 89%.It has 40 known functions contributing significantly to the sustenance of human life. A depletion in SA to <2.2g/dl, in most clinical settings worldwide, leads to loss of oncotic pressure of blood causing clinical manifestations of bipedal Oedema, in which the patients remain conscious. SA also contributes significantly to buffering of blood to a life-sustaining pH of 7.35-7.45. A drop in blood pH to <6.9 will lead to instant coma and death, which can occur after SA continues to deplete after manifestations of bipedal Oedema. In an intervention study conducted in 2014 following the discovery that “SA is depleted during malaria fever”, a Nutraceutical formulated for use as treatment adjunct to prevent SA depletions during malaria to <2.4g/dl after Efficacy testing was found to be satisfactory. There are five known types of Malaria caused by Apicomplexan parasites, Plasmodium: the most lethal being that caused by Plasmodium falciparum causing malignant tertian malaria, in which the fever was occurring every 48 hours coincides with the dumping of malaria-toxins (Hemozoin) into blood, causing contamination: blood must remain sterile. Other Apicomplexan parasites, Toxoplasma and Cryptosporidium, are opportunistic infections of HIV. Separate studies showed SA depletions in MDRTB (multidrug resistant TB), and MDRTB-HIV patients by the same mechanism discovered with malaria and such depletions will be further complicated whenever Apicomplexan parasitic infections co-exist. Both Apicomplexan parasites and the TB parasite belong to the Obligate-group of Parasites, which are parasites that replicate only inside its host; and most of them have capacities to over-consume host nutrients during parasitaemia. In MDRTB patients the body attempts repeatedly to prevent depletions in SA to critical levels in the presence of adequate nutrients and only for a while in MDRTB-HIV patients. These groups of patients will, therefore, benefit from the already tested Nutraceutical in malaria patients. The Nutraceutical bio-Powder was formulated (to BP 1988 specification) from twelve nature-based food-grade nutrients containing all dedicated nutrients for ensuring improved synthesis of Albumin by the liver. The Nutraceutical was administered daily for 38±2days in 23 children, in a prospective phase-2 clinical trial, and its impact on body weight and core blood parameters were documented at the start and end of efficacy testing period. Sixteen children who did not experience malaria-induced depletions of SA had significant SA increase; seven children who experienced malaria-induced depletions of SA had insignificant SA decrease. The Packed Cell Volume Percentage (PCV %), a measure of the Oxygen carrying capacity of blood and the amount of nutrients the body can absorb, increased in both groups. The total serum proteins (SA+ Globulins) increased or decreased within the continuum of normal. In conclusion, MDRTB and MDRTB-HIV patients will benefit from a variant of this Nutraceutical when used as treatment adjunct.Keywords: antitrypsin-free Nutraceutical, apicomplexan parasites, no predilections for low serum albumin, toxoplasmosis
Procedia PDF Downloads 288267 A Greener Approach towards the Synthesis of an Antimalarial Drug Lumefantrine
Authors: Luphumlo Ncanywa, Paul Watts
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Malaria is a disease that kills approximately one million people annually. Children and pregnant women in sub-Saharan Africa lost their lives due to malaria. Malaria continues to be one of the major causes of death, especially in poor countries in Africa. Decrease the burden of malaria and save lives is very essential. There is a major concern about malaria parasites being able to develop resistance towards antimalarial drugs. People are still dying due to lack of medicine affordability in less well-off countries in the world. If more people could receive treatment by reducing the cost of drugs, the number of deaths in Africa could be massively reduced. There is a shortage of pharmaceutical manufacturing capability within many of the countries in Africa. However one has to question how Africa would actually manufacture drugs, active pharmaceutical ingredients or medicines developed within these research programs. It is quite likely that such manufacturing would be outsourced overseas, hence increasing the cost of production and potentially limiting the full benefit of the original research. As a result the last few years has seen major interest in developing more effective and cheaper technology for manufacturing generic pharmaceutical products. Micro-reactor technology (MRT) is an emerging technique that enables those working in research and development to rapidly screen reactions utilizing continuous flow, leading to the identification of reaction conditions that are suitable for usage at a production level. This emerging technique will be used to develop antimalarial drugs. It is this system flexibility that has the potential to reduce both the time was taken and risk associated with transferring reaction methodology from research to production. Using an approach referred to as scale-out or numbering up, a reaction is first optimized within the laboratory using a single micro-reactor, and in order to increase production volume, the number of reactors employed is simply increased. The overall aim of this research project is to develop and optimize synthetic process of antimalarial drugs in the continuous processing. This will provide a step change in pharmaceutical manufacturing technology that will increase the availability and affordability of antimalarial drugs on a worldwide scale, with a particular emphasis on Africa in the first instance. The research will determine the best chemistry and technology to define the lowest cost manufacturing route to pharmaceutical products. We are currently developing a method to synthesize Lumefantrine in continuous flow using batch process as bench mark. Lumefantrine is a dichlorobenzylidine derivative effective for the treatment of various types of malaria. Lumefantrine is an antimalarial drug used with artemether for the treatment of uncomplicated malaria. The results obtained when synthesizing Lumefantrine in a batch process are transferred into a continuous flow process in order to develop an even better and reproducible process. Therefore, development of an appropriate synthetic route for Lumefantrine is significant in pharmaceutical industry. Consequently, if better (and cheaper) manufacturing routes to antimalarial drugs could be developed and implemented where needed, it is far more likely to enable antimalarial drugs to be available to those in need.Keywords: antimalarial, flow, lumefantrine, synthesis
Procedia PDF Downloads 202266 Extracorporeal Shock Wave Therapy versus Functional Electrical Stimulation on Spasticity, Function and Gait Parameters in Hemiplegic Cerebral Palsy
Authors: Mohamed A. Eid, Sobhy M. Aly
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Background: About 75% of children with spastic hemiplegic cerebral palsy walk independently, but most still show abnormal gait patterns because of contractures across the joints and muscle spasticity. Objective: The purpose of this study was to investigate and compare the effects of extracorporeal shock wave therapy (ESWT) versus functional electrical stimulation (FES) on spasticity, function, and gait parameters in children with hemiplegic cerebral palsy (CP). Methods: A randomized controlled trail was conducted for 45 children with hemiplegic CP ranging in age from 6 to 9 years. They were assigned randomly using opaque envelopes into three groups. Physical Therapy (PT) group consisted of 15 children and received the conventional physical therapy program (CPTP) in addition to ankle foot orthosis (AFO). ESWT group consisted of 15 children and received the CPTP, AFO in addition to ESWT. FES group also consisted of 15 children and received the CPTP, AFO in addition to FES. All groups received the program of treatment 3 days/week for 12 weeks. Evaluation of spasticity by using the Modified Ashworth Scale (MAS), function by using the Pediatric Evaluation Disability Inventory (PEDI) and gait parameters by using the 3-D gait analysis was conducted at baseline and after 12 weeks of the treatment program. Results: Within groups, significant improvements in spasticity, function, and gait (P = 0.05) were observed in both ESWT and FES groups after treatment. While between groups, ESWT group showed significant improvements in all measured variables compared with FES and PT groups (P ˂ 0.05) after treatment. Conclusion: ESWT induced significant improvement than FES in decreasing spasticity and improving function and gait in children with hemiplegic CP. Therefore, ESWT should be included as an adjunctive therapy in the rehabilitation program of these children.Keywords: cerebral palsy, extracorporeal shock wave therapy, functional electrical stimulation, function, gait, spasticity
Procedia PDF Downloads 130265 Neuroprotective Effects of Allium Cepa Extract Against Ischemia Reperfusion Induced Cognitive Dysfunction and Brain Damage in Mice
Authors: Jaspal Rana
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Oxidative stress has been identified as an underlying cause of ischemia-reperfusion (IR) related cognitive dysfunction and brain damage. Therefore, antioxidant based therapies to treat IR injury are being investigated. Allium cepa L. (onion) is used as culinary medicine and is documented to have marked antioxidant effects. Hence, the present study was designed to evaluate the effect of A. cepa outer scale extract (ACE) against IR induced cognition and biochemical deficit in mice. ACE was prepared by maceration with 70% methanol and fractionated into ethylacetate and aqueous fractions. Bilateral common carotid artery occlusion for 10 min followed by 24 h reperfusion was used to induce cerebral IR injury. Following IR injury, ACE (100 and 200 mg/kg) was administered orally to animals for 7 days once daily. Behavioral outcomes (memory and sensorimotor functions) were evaluated using Morris water maze and neurological severity score. Cerebral infarct size, brain thiobarbituric acid reactive species, reduced glutathione, and superoxide dismutase activity was also determined. Treatment with ACE significantly ameliorated IR mediated deterioration of memory and sensorimotor functions and rise in brain oxidative stress in animals. The results of the present investigation revealed that ACE improved functional outcomes after cerebral IR injury which may be attributed to its antioxidant properties.Keywords: ischemia-reperfusion, neuroprotective, stroke, antioxidant
Procedia PDF Downloads 115264 NMR-Based Metabolomic Study of Antimalarial Plant Species Used Traditionally by Vha-Venda People in Limpopo Province, South Africa
Authors: Johanna Bapela, Heino Heyman, Marion Meyer
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Regardless of the significant advances accomplished in reducing the burden of malaria and other tropical diseases in recent years, malaria remains a major cause of mortality in endemic countries. This is especially the case in sub-Saharan Africa where 99% of the estimated global malaria deaths occurs on an annual basis. The emergence of resistant Plasmodium species and the lack of diversified chemotherapeutic agents provide the rationale for bioprospecting for antiplasmodial scaffolds. Crude extracts from twenty indigenous antimalarial plant species were screened for antimalarial activity and then subjected to 1H NMR-based metabolomic analysis. Ten plant extracts exhibited significant in vitro antiplasmodial activity (IC50 ≤ 5 µg/ml). The Principal Component Analysis (PCA) of the acquired 1H NMR spectra could not separate the analyzed plant extracts according to the detected antiplasmodial bioactivity. Application of supervised Orthogonal Projections to Latent Structures–Discriminant Analysis (OPLS-DA) to the 1H NMR profiles resulted in a discrimination pattern that could be correlated to bioactivity. A contribution plot generated from the OPLS-DA scoring plot illustrated the classes of compounds responsible for the observed grouping. Given the preliminary in vitro results, Tabernaemontana elegans Stapf. (Apocynaceae) and Vangueria infausta Burch. subsp. infausta (Rubiaceae) were subjected to further phytochemical investigations. Two indole alkaloids, dregamine and tabernaemontanine possessing antiplasmodial activity were isolated from T. elegans. Two compounds were isolated from V. infausta subsp. infausta and identified as friedelin (IC50 = 3.01 µg/ml) and morindolide (IC50 = 18.5 µg/ml). While these compounds have been previously identified, this is the first account of their occurrence in the genus Vangueria and their antiplasmodial activity. Based on the results of the study, metabolomics can be used to globally identify classes of plant secondary metabolites that are responsible for antiplasmodial activity.Keywords: ethnopharmacology, Malaria, medicinal plants, metabolomics
Procedia PDF Downloads 341263 Stability Analysis of a Human-Mosquito Model of Malaria with Infective Immigrants
Authors: Nisha Budhwar, Sunita Daniel
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In this paper, we analyse the stability of the SEIR model of malaria with infective immigrants which was recently formulated by the authors. The model consists of an SEIR model for the human population and SI Model for the mosquitoes. Susceptible humans become infected after they are bitten by infectious mosquitoes and move on to the Exposed, Infected and Recovered classes respectively. The susceptible mosquito becomes infected after biting an infected person and remains infected till death. We calculate the reproduction number R0 using the next generation method and then discuss about the stability of the equilibrium points. We use the Lyapunov function to show the global stability of the equilibrium points.Keywords: equilibrium points, exposed, global stability, infective immigrants, Lyapunov function, recovered, reproduction number, susceptible
Procedia PDF Downloads 365262 In Silico Studies on Selected Drug Targets for Combating Drug Resistance in Plasmodium Falcifarum
Authors: Deepika Bhaskar, Neena Wadehra, Megha Gulati, Aruna Narula, R. Vishnu, Gunjan Katyal
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With drug resistance becoming widespread in Plasmodium falciparum infections, development of the alternative drugs is the desired strategy for prevention and cure of malaria. Three drug targets were selected to screen promising drug molecules from the GSK library of around 14000 molecules. Using an in silico structure-based drug designing approach, the differences in binding energies of the substrate and inhibitor were exploited between target sites of parasite and human to design a drug molecule against Plasmodium. The docking studies have shown several promising molecules from GSK library with more effective binding as compared to the already known inhibitors for the drug targets. Though stronger interaction has been shown by several molecules as compare to reference, few molecules have shown the potential as drug candidates though in vitro studies are required to validate the results.Keywords: plasmodium, malaria, drug targets, in silico studies
Procedia PDF Downloads 446261 Analysis of a Differential System to Get Insights on the Potential Establishment of Microsporidia MB in the Mosquito Population for Malaria Control
Authors: Charlene N. T. Mfangnia, Henri E. Z. Tonnang, Berge Tsanou, Jeremy Herren
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Microsporidia MB is a recently discovered symbiont capable of blocking the transmission of Plasmodium from mosquitoes to humans. The symbiont can spread both horizontally and vertically among the mosquito population. This dual transmission gives the symbiont the ability to invade the mosquito population. The replacement of the mosquito population by the population of symbiont-infected mosquitoes then appears as a promising strategy for malaria control. In this context, the present study uses differential equations to model the transmission dynamics of Microsporidia MB in the population of female Anopheles mosquitoes. Long-term propagation scenarios of the symbiont, such as extinction, persistence or total infection, are obtained through the determination of the target and basic reproduction numbers, the equilibria, and the study of their stability. The stability is illustrated numerically, and the contribution of vertical and horizontal transmission in the spread of the symbiont is assessed. Data obtained from laboratory experiments are then used to explain the low prevalence observed in nature. The study also shows that the male death rate, the mating rate and the attractiveness of MB-positive mosquitoes are the factors that most influence the transmission of the symbiont. In addition, the introduction of temperature and the study of bifurcations show the significant influence of the environmental condition in the propagation of Microsporidia MB. This finding proves the necessity of taking into account environmental variables for the potential establishment of the symbiont in a new area.Keywords: differential equations, stability analysis, malaria, microsporidia MB, horizontal transmission, vertical transmission, numerical illustration
Procedia PDF Downloads 113260 Outcome of Patients Undergoing Hemicraniectomy for Malignant Middle Cerebral Artery Infarction: A 5 Year Retrospective Study at Perpetual Succour Hospital, Cebu City, Philippines
Authors: Adelson G. Guillarte, M. D., Noel J. Belonguel, Jarungchai Anton S. Vatanagul
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Patients with malignant middle cerebral infarction (MCA) (with massive brain swelling and herniation) were reported to have a mortality rate of 80% even with the appropriate conservative medical therapy. European Trials (DECIMAL, DESTINY I, and II, HAMLET) showed significant improvement in mortality and functional outcome with hemicraniectomy. No known published local studies in the region, thus a local study is vital. This is a single center, retrospective, descriptive, cross-sectional, chart review study which includes ≥18 year-old patients with malignant MCA infarction, who underwent hemicraniectomy, and those who were given conservative medical therapy alone, from January 2008 to December 2012 at Perpetual Succour Hospital. Excluded were patients whose charts are with insufficient data, prior MCA stroke, with concomitant intracerebral hemorrhage and with other serious medical conditions or terminal illnesses. Minimum of 32 populations were needed. Data were presented in mean, standard deviation, frequency and percentage distribution. Man n Whitney U test and Chi Square test were used. P-values lesser than 0.05 alpha were considered statistically significant. A total of 672 stroke patients were admitted. 34 patients pass the inclusion criteria. 9 underwent hemicraniectomy and 25 were treated by conservative medical therapy alone. Although not statistically significant (64% vs 33%, p=0.112) there were more patients noted improved in the conservative treatment group. Meanwhile, the Hemicraniectomy group have increased percentage of mortality (67%) (p=0.112). There was a decreasing trend in the average NIHSS score in both groups from admission to post-op 7 days (p=0.198, p=0.78). A bigger multicenter prospective study is recommended to control inherent biases and limitations of a retrospective and smaller study.Keywords: cerebral infarct, hemicraniectomy, ischemic stroke, malignant middle cerebral artery (MCA) infarct
Procedia PDF Downloads 317259 Reversible Cerebral Vasoconstriction Syndrome at Emergency Department
Authors: Taerim Kim, Shin Ahn, Chang Hwan Sohn, Dong Woo Seo, Won Young Kim
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Object: Reversible cerebral vasospasm syndrome (RCVS) remains an underrated cause of thunderclap headache which shares similar history of the ‘worst-ever’ headache with subarachnoid hemorrhage (SAH) to the emergency physicians. This study evaluated the clinical manifestations, radiological features, and outcomes of patients with RCVS so that the physicians could raise the high index of suspicion to detect RCVS in more patients with thunderclap headache before having life-threatening complications. Methods: The electric medical records of 18 patients with diagnostic criteria of RCVS at the emergency department (ED) between January 2013 and December 2014 were retrospective reviewed. Results: The mean age was 50.7 years, and 80% were women. Patients with RCVS visit an average of 4.7 physicians before receiving an accurate diagnosis and mean duration of symptom until diagnosis is 9.3 days. All patients except one experienced severe headache, from 8 to 10 pain intensity on a numerical rating scale (NRS). 44% of patients had nausea as an associated symptom, 66% of patients experienced worsening of headache while gagging, leaning forward, defecating, urinating or having sex. The most frequently affected vessels are middle cerebral arteries demonstrating the characteristic diffuse “string of beads” appearance. Four patients had SAH as a complication. Conclusion: Patients with RCVS have a unique set of clinical and imaging features. Emergency physicians should raise the high index of suspicion to detect RCVS in more patients with thunderclap headache before life-threatening complications.Keywords: headache, thunderclap, subarachnoid haemorrhage, stroke
Procedia PDF Downloads 427258 Bacterial Causes of Cerebral Abscess and Impact on Long Term Patient Outcomes
Authors: Umar Rehman, Holly Roy, K. T. Tsang, D. S. Jeyaretna, W Singleton, B. Fisher, P. A. Glew, J. Greig, Peter C. Whitfield
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Introduction: A brain abscess is a life-threatening condition, carrying significant mortality. It requires rapid identification and treatment. Management involves a combination of antibiotics and surgery. The aim of the current study was to identify common bacteria responsible for cerebral abscesses as well as the long term functional and neurological outcomes of patients following treatment in a retrospective series at a single UK neurosurgical centre. Methodology: We analysed patients that had received a diagnosis of 'cerebral abscess' or 'subdural empyema' between June 2002 and June 2018. This was done in the form of a retrospective review. The search resulted in a total of 180 patients; with 37 patients being excluded (spinal abscess, below 18 or non-abscess related admissions). Data were collected from medical case notes including information about demographics, comorbidities, immunosuppression, presentation, size/location of lesions, pathogens, treatment, and outcomes. Results: In total, we analysed 143 patients between the ages of 18-90. Focal neurological deficit and headaches were seen in 84% and 68% of patients respectively. 108 positive brain cultures were seen; with the largest proportion, 59.2% being gram-positive cocci, with strep intermedius being the most common pathogen identified in 13.9% of patients. Of the patients with positive blood cultures (n=11), 72.7% showed the same organism both in the blood and on the brain cultures. Long term outcomes (n=72) revealed that 48% of patients seizure-free without requiring anti-epileptics, 51.3% of patients had full recovery of their neurological symptoms. There was a mortality rate of 13.9% in the series. Conclusion: In conclusion, the largest bacterial cause of abscess within our population was due to gram-positive cocci. The majority of the patient demonstrated full neurological recovery with close to half of patients not requiring anti-epileptics following discharge.Keywords: bacteria, cerebral abscess, long term outcome, neurological deficit
Procedia PDF Downloads 119257 Designing and Using a 3-D Printed Dynamic Upper Extremity Orthosis (DUEO) with Children with Cerebral Palsy and Severe Upper Extremity Involvement
Authors: Justin Lee, Siraj Shaikh, Alice Chu MD
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Children with cerebral palsy (CP) commonly present with upper extremity impairment, affecting one or both extremities, and are classified using the Manual Ability Classification Scale (MACS). The MACS defines bimanual hand abilities for children ages 4-18 years in everyday tasks and is a gradient scale, with I being nearly normal and V requiring total assistance. Children with more severe upper extremity impairment (MACS III-V) are often underrepresented, and relatively few effective therapies have been identified for these patients. Current orthoses are static and are only meant to prevent the progression of contractures in these patients. Other limitations include cost, comfort, accessibility, and longevity of the orthoses. Taking advantage of advances in 3D printing technology, we have created a highly customizable upper extremity orthotic that can be produced at a low cost. Iterations in our design have resulted in an orthotic that is custom fit to the patient based on scans of their arm, made of rigid polymer when needed to provide support, flexible material where appropriate to allow for comfort, and designed with a mechanical pulley system to allow for some functional use of the arm while in the orthotic. Preliminary data has shown that our orthotic can be built at a fraction of the cost of current orthoses and provide clinically significant improvement in assisting hand assessment (AHA) and pediatric quality of life scores (PedsQL).Keywords: upper extremity orthosis, upper extremity, orthosis, 3-D printing, cerebral palsy, occupational therapy, spasticity, customizable
Procedia PDF Downloads 307256 The 10,000 Fold Effect of Retrograde Neurotransmission: A New Concept for Cerebral Palsy Revival by the Use of Nitric Oxide Donars
Authors: V. K. Tewari, M. Hussain, H. K. D. Gupta
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Background: Nitric Oxide Donars (NODs) (intrathecal sodium nitroprusside (ITSNP) and oral tadalafil 20mg post ITSNP) has been studied in this context in cerebral palsy patients for fast recovery. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a) Retrograde Neurotransmission (acute cases): 1) Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2) Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b) Vasopasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c) Long-Term Potentiation (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Design: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat cerebral palsy cases. Case-control prospective study. Materials and Methods: The experimental population included 82 cerebral palsy patients (10 patients were given control treatments without NOD or with 5% dextrose superfusion, and 72 patients comprised the NOD group). The mean time for superfusion was 5 months post-cerebral palsy. Pre- and post-NOD status was monitored by Gross Motor Function Classification System for Cerebral Palsy (GMFCS), MRI, and TCD studies. Results: After 7 days in the NOD group, the mean change in the GMFCS score was an increase of 1.2 points mean; after 3 months, there was an increase of 3.4 points mean, compared to the control-group increase of 0.1 points at 3 months. MRI and TCD documented the improvements. Conclusions: NOD (ITSNP boosts up the recovery and oral tadalafil maintains the recovery to a well-desired level) acts swiftly in the treatment of CP, acting within 7 days on 5 months post-cerebral palsy either of the three mechanisms.Keywords: cerebral palsy, intrathecal sodium nitroprusside, oral tadalafil, perforators, vasodilations, retrograde transmission, the 10, 000-fold effect, long-term potantiation
Procedia PDF Downloads 362255 Pontine and Lobar Hemorrhage from Venous Infarction secondary to Cerebral Venous Thrombosis in a 70-year old Filipina with Protein S Deficiency: A Case Report
Authors: Michelangelo Liban, Debbie Liquete
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A 70-year-old right-handed Filipina was seen by the Neurology service due to a new onset headache, bi-occipital in location, dull squeezing in character with a pain score of 8/10 with associated nausea and one episode of non-projectile, which provided no relief. Due to the alarming features of the headache despite the absence of risk factors and an essentially normal neurologic examination, a cranial CTA+CTV was done, which revealed a small left frontal and small right pontine hyper density with minimal perilesional edema. Findings also revealed filling defects in the straight and right transverse sinus and a consideration of hypoplastic left transverse sinus with no definite evidence of aneurysm nor A-V malformation. She had normal levels of D-Dimer, Protein C, ANA and Anti-DS DNA but had a low Protein S of 56% (N.V is 70-120%). Antithrombin, homocysteine and Factor V Leiden were not done due to unavailability of the tests. She was then treated as a case of Cerebral Venous Thrombosis with multiple hemorrhage from venous infraction and was given anticoagulants which provided relief of the headache. She did not manifest with any further cortical, bulbar or sensorimotor deficits hence was discharged improved after 15 hospital days. To our knowledge, there are no case reports of patients with CVT from Protein S deficiency and venous anomaly that presented with multiple hemorrhage from venous infarction, more so affecting the brainstem. In this paper, a rare location of CVT in a newly diagnosed Protein S deficient patient is presented together with an uneventful course and favorable outcome.Keywords: protein S deficiency, cerebral venous thrombosis, pontine hemorrhage from venous infarction, elderly
Procedia PDF Downloads 75254 Allium Cepa Extract Provides Neuroprotection Against Ischemia Reperfusion Induced Cognitive Dysfunction and Brain Damage in Mice
Authors: Jaspal Rana, Alkem Laboratories, Baddi, Himachal Pradesh, India Chitkara University, Punjab, India
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Oxidative stress has been identified as an underlying cause of ischemia-reperfusion (IR) related cognitive dysfunction and brain damage. Therefore, antioxidant based therapies to treat IR injury are being investigated. Allium cepa L. (onion) is used as culinary medicine and is documented to have marked antioxidant effects. Hence, the present study was designed to evaluate the effect of A. cepa outer scale extract (ACE) against IR induced cognition and biochemical deficit in mice. ACE was prepared by maceration with 70% methanol and fractionated into ethylacetate and aqueous fractions. Bilateral common carotid artery occlusion for 10 min followed by 24 h reperfusion was used to induce cerebral IR injury. Following IR injury, ACE (100 and 200 mg/kg) was administered orally to animals for 7 days once daily. Behavioral outcomes (memory and sensorimotor functions) were evaluated using Morris water maze and neurological severity score. Cerebral infarct size, brain thiobarbituric acid reactive species, reduced glutathione, and superoxide dismutase activity was also determined. Treatment with ACE significantly ameliorated IR mediated deterioration of memory and sensorimotor functions and rise in brain oxidative stress in animals. The results of the present investigation revealed that ACE improved functional outcomes after cerebral IR injury, which may be attributed to its antioxidant properties.Keywords: stroke, neuroprotection, ischemia reperfusion, herbal drugs
Procedia PDF Downloads 106253 Knowledge Based Software Model for the Management and Treatment of Malaria Patients: A Case of Kalisizo General Hospital
Authors: Mbonigaba Swale
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Malaria is an infection or disease caused by parasites (Plasmodium Falciparum — causes severe Malaria, plasmodium Vivax, Plasmodium Ovale, and Plasmodium Malariae), transmitted by bites of infected anopheles (female) mosquitoes to humans. These vectors comprise of two types in Africa, particularly in Uganda, i.e. anopheles fenestus and Anopheles gambaie (‘example Anopheles arabiensis,,); feeds on man inside the house mainly at dusk, mid-night and dawn and rests indoors and makes them effective transmitters (vectors) of the disease. People in both urban and rural areas have consistently become prone to repetitive attacks of malaria, causing a lot of deaths and significantly increasing the poverty levels of the rural poor. Malaria is a national problem; it causes a lot of maternal pre-natal and antenatal disorders, anemia in pregnant mothers, low birth weights for the newly born, convulsions and epilepsy among the infants. Cumulatively, it kills about one million children every year in sub-Saharan Africa. It has been estimated to account for 25-35% of all outpatient visits, 20-45% of acute hospital admissions and 15-35% of hospital deaths. Uganda is the leading victim country, for which Rakai and Masaka districts are the most affected. So, it is not clear whether these abhorrent situations and episodes of recurrences and failure to cure from the disease are a result of poor diagnosis, prescription and dosing, treatment habits and compliance of the patients to the drugs or the ethical domain of the stake holders in relation to the main stream methodology of malaria management. The research is aimed at offering an alternative approach to manage and deal absolutely with problem by using a knowledge based software model of Artificial Intelligence (Al) that is capable of performing common-sense and cognitive reasoning so as to take decisions like the human brain would do to provide instantaneous expert solutions so as to avoid speculative simulation of the problem during differential diagnosis in the most accurate and literal inferential aspect. This system will assist physicians in many kinds of medical diagnosis, prescribing treatments and doses, and in monitoring patient responses, basing on the body weight and age group of the patient, it will be able to provide instantaneous and timely information options, alternative ways and approaches to influence decision making during case analysis. The computerized system approach, a new model in Uganda termed as “Software Aided Treatment” (SAT) will try to change the moral and ethical approach and influence conduct so as to improve the skills, experience and values (social and ethical) in the administration and management of the disease and drugs (combination therapy and generics) by both the patient and the health worker.Keywords: knowledge based software, management, treatment, diagnosis
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